Allergic rhinitis (AR) is a chronic inflammatory disease of the upper airways which is a worldwide health problem that generates a significant healthcare burden in adults, adolescents, and children. AR currently affects up to 40 % of the worldwide population, affecting overall quality of life as patients’ experience fatigue, sleep disturbance, social function impairment, anxiety, learning and attention impairment, depressed mood and decreased productivity. In India, the burden of AR is enormous, constituting about 55% of all allergies. Reported incidence of AR in India ranges between 20% and 30%.
The allergic response in AR occurs in two phases, the “early” and “late” phase responses. Early phase response occurs within minutes of exposure to the allergen and tends to produce sneezing, itching, and clear rhinorrhoea. Late phase response occurs 4 to 8 hours after allergen exposure and is characterized by congestion and inflammation. Oral antihistamines are a convenient choice of treatment out of all available therapeutic options for patients with AR. The older first-generation antihistamines are effective at controlling the symptoms of AR but are associated with significant adverse effects, such as sedation and anticholinergic effects making them a less attractive therapeutic option. Second-generation antihistamines were developed to provide efficacious treatment while decreasing adverse effects associated with first-generation agents. Several treatment guidelines have recommended the use of second generation antihistamines as the first line of treatment for allergic rhinitis and urticaria. Bilastine is the most modern drug in this group, approved in India in 2019.
Bilastine is a novel, second-generation antihistamine approved for its use in adults at the therapeutic dose of 20 mg OD for the treatment of allergic rhinoconjuctivitis and urticaria. It is a potent H1-antihistamine with a high selectivity for H1 receptors and poor affinity to 30 other receptors. Bilastine has been shown to have rapid onset of action within 45 minutes and has a long duration of action which lasts for at-least 26 hours. Bilastine is efficacious in reducing all nasal symptoms including obstruction and eye symptoms. It has also been shown to have anti-inflammatory properties.
Bilastine has shown excellent safety in patients of allergic rhinitis. It has minimal capacity to cause CNS adverse effects as it has the lowest rate of brain H1 receptor occupancy of all the available antihistamines. In addition to being non-sedating, bilastine is free of cardiotoxicity; it is the only commercially available AH that has been tested using the stringent ICH E/14 criteria. Bilastine bypasses the CYP enzyme system thus reducing its potential to cause drug-drug interactions. Also, its poor affinity to other receptors makes it free of anticholinergic side effects. Bilastine does not result weight gain thus giving additional benefit.
Bilastine indeed epitomizes the evolution of research on antihistamines. It in-fact has the highest number of desired features for a modern antihistamine according to international ARIA guidelines.
BILLARGIC (Bilastine tablets 20 mg) by Cipla is available as a blister pack of 10 tablets.
Each uncoated tablet contains:
Bilastine ……………………………20 mg
Tablets for oral use
Bilastine is a non-sedating, long-acting histamine antagonist with selective peripheral H1 receptor antagonist affinity and no affinity for muscarinic receptors.
Bilastine inhibited histamine-induced wheal and flare skin reactions for 24 hours following single doses
Bilastine is rapidly absorbed after oral administration with a time to maximum plasma concentration of around 1.3 hours. No accumulation was observed. The mean value of Bilastine oral bioavailability is 61%.
In vitro and in vivo studies have shown that bilastine is a substrate of P-gp and OATP. Bilastine does not appear to be a substrate of the transporter BCRP (Breast cancer resistance proteins) or renal transporters OCT2, OAT1 and OAT3. Based on in vitro studies, Bilastine is not expected to inhibit the following transporters in the systemic circulation: P-gp, MRP2, BCRP, BSEP, OATP1B1, OATP1B3, OATP2B1, OAT1, OAT3, OCT1, OCT2, and NTCP, since only mild inhibition was detected for P-gp, OATP2B1 and OCT1, with an estimated IC50 ≥ 300 μM, much higher than the calculated clinical plasma Cmax and therefore these interactions will not be clinically relevant. However, based on these results inhibition by bilastine of transporters present in the intestinal mucosa, e.g. P-gp, cannot be excluded. At therapeutic doses bilastine is 84-90% bound to plasma proteins.
Bilastine did not induce or inhibit activity of CYP450 isoenzymes in in vitro studies.
In a mass balance study performed in healthy volunteers, after administration of a single dose of 20 mg 14C-Bilastine, almost 95% of the administered dose was recovered in urine (28.3%) and faeces (66.5%) as unchanged Bilastine, confirming that Bilastine is not significantly metabolized in humans. The mean elimination half-life calculated in healthy volunteers was 14.5 h.
Bilastine presents linear pharmacokinetics in the dose range studied (5 to 220 mg), with a low interindividual variability.
Bilastine tablet is indicated for symptomatic treatment of allergic rhino-conjunctivitis (seasonal and perennial) and urticaria in adults.
One tablet (20 mg) once daily for the relief of symptoms of allergic rhino-conjunctivitis (seasonal and perennial) and urticaria in adults. The tablet should be taken by oral route one hour before or two hours after intake of food or fruit juice.
Duration of Treatment
For allergic rhinitis the treatment should be limited to the period of exposure to allergens. For seasonal allergic rhinitis treatment could be discontinued after the symptoms have resolved and reinitiated upon their reappearance. In perennial allergic rhinitis continued treatment may be proposed to the patients during the allergen exposure periods. For urticaria the duration of treatment depends on the type, duration and course of the complaints.
Method of Administration
The tablet is to be swallowed with water. It is recommended to take the daily dose in one single intake.
Hypersensitivity to the active substance or to any of the excipients
Efficacy and safety of bilastine in children under 12 years of age have not been established.
In patients with moderate or severe renal impairment co-administration of bilastine with P-glycoprotein inhibitors, such as e.g, ketoconazole, erythromycin, cyclosporine, ritonavir or diltiazem, may increase plasmatic levels of bilastine and therefore increase the risk of adverse effects of bilastine. Therefore, co-administration of bilastine and P-glycoprotein inhibitors should be avoided in patients with moderate or severe renal impairment.
Interaction with Ketoconazole or Erythromycin
Concomitant intake of Bilastine and ketoconazole or erythromycin increased Bilastine AUC 2-fold and Cmax 2-3 fold. These changes can be explained by interaction with intestinal efflux transporters, since Bilastine is substrate for P-gp and not metabolized. These changes do not appear to affect the safety profile of Bilastine and ketoconazole or erythromycin, respectively. Other medicinal products that are substrates or inhibitors of P-gp, such as cyclosporine, may likewise have the potential to increase plasma concentrations of bilastine.
Interaction with Diltiazem
Concomitant intake of Bilastine 20 mg and Diltiazem 60 mg increased Cmax of Bilastine by 50%. This effect can be explained by interaction with intestinal efflux transporters, and does not appear to affect the safety profile of bilastine.
Interaction with Lorazepam
Concomitant intake of Bilastine 20 mg and lorazepam 3 mg for 8 days did not potentiate the depressant CNS effects of lorazepam.
Interaction with Alcohol
The psychomotor performance after concomitant intake of alcohol and 20 mg Bilastine was similar to that observed after intake of alcohol and placebo.
Interaction with Grapefruit Juice
Concomitant intake of Bilastine 20 mg and grapefruit juice decreased Bilastine bioavailability by 30%. This effect may also apply to other fruit juices. The degree of bioavailability decrease may vary between producers and fruits. The mechanism for this interaction is an inhibition of OATP1A2, an uptake transporter for which Bilastine is a substrate. Medicinal products that are substrates or inhibitors of OATP1A2, such as ritonavir or rifampicin, may likewise have the potential to decrease plasma concentrations of bilastine.
Interaction with Food
Food significantly reduces the oral bioavailability of bilastine by 30%.
Interaction studies have only been performed in adults. Extent of interaction with other medicinal products and other forms of interaction is expected to be similar in paediatric population from 12 to 17 years of age.
No dosage adjustment is required in patients with renal impairment.
There is no clinical experience in patients with hepatic impairment. Since bilastine is not metabolized and renal clearance is its major elimination route, hepatic impairment is not expected to increase systemic exposure above the safety margin. Therefore, no dosage adjustment is required in patients with hepatic impairment.
There are no adequate and well controlled studies on pregnancy outcome with bilastine in pregnant women.
Studies in animals do not indicate direct or indirect harmful effects with respect to reproductive toxicity, parturition or postnatal development. As a precautionary measure, it is preferable to avoid the use of bilastine during pregnancy.
There are no or limited amount of clinical data on fertility. A study in rats did not indicate any negative effect on fertility.
The excretion of bilastine in milk has not been studied in humans. Available pharmacokinetic data in animals have shown excretion of bilastine in milk.
A decision on whether to discontinue/abstain from bilastine therapy must be made taking into account the benefit of breast-feeding for the child and the benefit of bilastine therapy for the mother.
The safety and efficacy of bilastine in children under 12 years of age have not yet been established.
No dosage adjustments are required in elderly patients.
The below adverse effects were determined based on data from the Bilastine clinical studies and frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).
Infections and Infestations
Uncommon: Oral herpes
Metabolism and Nutrition Disorders
Uncommon: Increased appetite
Uncommon: Anxiety, insomnia
Ear and Labyrinth Disorders
Uncommon: Tinnitus, vertigo
Uncommon: Right bundle branch block, sinus arrhythmia, other ECG abnormalities, electrocardiogram QT prolonged
Nervous System Disorders
Common: Somnolence, headache
Respiratory, Thoracic and Mediastinal Disorders
Uncommon: Dyspnea, nasal discomfort, nasal dryness
Uncommon: Upper abdominal pain, nausea, stomach discomfort, diarrhea, dry mouth, dyspepsia and gastritis
Skin and Subcutaneous Tissue Disorders
General Disorders and Administration Site Conditions
Uncommon: Fatigue, thirst, improved pre-existing condition, pyrexia and asthenia.
Uncommon: Increased gamma-glutamyltranferase, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, blood triglycerides increased and increased weight.
Frequency not known (cannot be estimated from the available data): Palpitations, tachycardia and hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnoea, rash, localised oedema/local swelling, and erythema) and vomiting have been observed during the post-marketing period.
Information regarding acute overdose of bilastine is retrieved from the experience of clinical trials conducted during the development and the post-marketing surveillance. In clinical trials, after administration of bilastine at doses 10 to 11 times the therapeutic dose (220 mg as single dose; or 200 mg/day for 7 days) to healthy volunteers frequency of treatment emergent adverse events was two times higher than with placebo. The adverse reactions most frequently reported were dizziness, headache and nausea. No serious adverse events and no significant prolongation in the QTc interval were reported. The information collected in the post-marketing surveillance is consistent with that reported in clinical trials.
Critical evaluation of bilastine's multiple dose (100 mg x4 days) effect on ventricular repolarization by a “thorough QT/QTc cross-over study” involving 30 healthy volunteers did not show significant QTc prolongation.
In the event of overdose symptomatic and supportive treatment is recommended.
There is no known specific antidote to bilastine. There is no known specific antidote to bilastine.
Store at a temperature not exceeding 30°C, protect from light and moisture.
Keep out of reach of children
Alu- Alu blister pack of 10 tablets
Last Updated: April 2019
Last Reviewed: April 2019